tbuckley/cabot-search huggingface dataset:
Late effects in survivors of infant acute lymphoblastic leukaemia—a study of the Australian and New Zealand Children’s Haematology/Oncology Group
Authors: Denitza Mironova, Chitra M. Saraswati, Peter Downie, Chow Yee Lai, Eleanor Cook, Vickyanne Carruthers, Perla Moukhaiber, Fiona Molloy, Joshua Serov, Elizabeth McKinnon, Frank Alvaro, Michael Osborn, Tamas Revesz, Tim Prestidge, Siobhan Cross, Caroline M. Bateman, Andrew S. Moore, Seong Lin Khaw, Marion K. Mateos, Rishi S. Kotecha
Journal: Blood Cancer Journal (2023)

Acute lymphoblastic leukaemia (ALL) in infancy, defined as ≤1 year of age at diagnosis, is rare with an incidence of 1.8 cases per 100,000 [1].KMT2A-gene rearrangements are present in up to 80% of infants with ALL and are associated with a poor prognosis.Historically, collaborative group treatment protocols have focused on intensification of conventional chemotherapy, which can include allogeneic haematopoietic stem cell transplant (HSCT) for high-risk infants, however outcomes for KMT2Arearranged infant ALL have remained poor due to high relapse rates and treatment-related mortality [2,3].Given the rarity of the patient population and low survival rates, there is limited data regarding long-term outcomes in survivors of infant ALL in the context of receiving intensive therapy to achieve a cure.We conducted a multi-centre retrospective analysis of all infants diagnosed with ALL in Australia and New Zealand from 1 January 1992 to 31 December 2011 (Human Research Ethics Approval RGS0000001383).Patients were identified from the cancer registry of every paediatric cancer centre in Australia and New Zealand and standardised data were captured for each patient until 28 February 2021, including demographics, disease characteristics, treatment, outcome, a systematic capture of late effects based on the Children's Oncology Group long-term followup guidelines (version 5.0) and date of last follow-up.Event-free survival (EFS) was defined as the time from ALL diagnosis to treatment failure or relapse, all-cause mortality, or second malignancy.Overall survival (OS) was defined as the time from diagnosis to all-cause mortality.Time was censored at the last follow-up if no events were recorded.All analyses were performed using R (version 4.2.2).Over the 20-year period, 119 infants were diagnosed with ALL in Australia and New Zealand.Treatment was administered according to US or European-based infant-specific collaborative group protocols available at the time of diagnosis.Fiveyear OS was 60.5% (SE 4.5) and 5-year EFS was 47.1% (SE 4.7) (Fig. 1; Supplementary Fig. 1).EFS and OS were adversely influenced by the presence of a KMT2A-rearrangement, age <6 months, central nervous system (CNS) involvement, high presenting white blood cell count and CD10-negative immunophenotype, with male sex also an adverse prognostic factor for EFS on univariate analysis (Table 1; Supplementary Fig. 2).Cox regression analysis, with EFS as an endpoint, identified presence of a KMT2A-rearrangement, age <6 months and male
BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps
Authors: Margaret E. Maes, Ryan J. Donahue, Cassandra L. Schlamp, Olivia J. Marola, Richard T. Libby, Robert W. Nickells
Journal: Molecular Neurodegeneration (2023)

Pro-apoptotic BAX is a central mediator of retinal ganglion cell (RGC) death after optic nerve damage. BAX activation occurs in two stages including translocation of latent BAX to the mitochondrial outer membrane (MOM) and then permeabilization of the MOM to facilitate the release of apoptotic signaling molecules. As a critical component of RGC death, BAX is an attractive target for neuroprotective therapies and an understanding of the kinetics of BAX activation and the mechanisms controlling the two stages of this process in RGCs is potentially valuable in informing the development of a neuroprotective strategy.
Re: Gabriela Ilie, Ricardo Rendon, Ross Mason, et al. A Comprehensive 6-mo Prostate Cancer Patient Empowerment Program Decreases Psychological Distress Among Men Undergoing Curative Prostate Cancer Treatment: A Randomized Clinical Trial. Eur Urol 2023;83:561–70
Authors: André Pontes-Silva
Journal: European Urology (2023)
Nivolumab Switch Maintenance Therapy After Tyrosine Kinase Inhibitor Induction in Metastatic Renal Cell Carcinoma: A Randomized Clinical Trial by the Interdisciplinary Working Group on Renal Tumors of the German Cancer Society (NIVOSWITCH; AIO-NZK-0116ass)
Authors: Viktor Grünwald, Philipp Ivanyi, Stefanie Zschäbitz, Manfred Wirth, Peter Staib, Martin Schostak, Philip Dargatz, Lothar Müller, Michael Metz, Lothar Bergmann, Thomas Steiner, Martin Welslau, Anja Lorch, Reza Rafiyan, Eva Hellmis, Cristopher Darr, Philipp Schütt, Johannes Meiler, Thomas Kretz, Wolfgang Loidl, Anne Flörcken, Martin Mänz, Axel Hinke, Arndt Hartmann, Carsten Grüllich
Journal: European Urology (2023)
Long-term utilization and benefit of luspatercept in transfusion-dependent, erythropoiesis-stimulating agent-refractory or -intolerant patients with lower-risk myelodysplastic syndromes with ring sideroblasts
Authors: Uwe Platzbecker, Valeria Santini, Rami S. Komrokji, Amer M. Zeidan, Guillermo Garcia-Manero, Rena Buckstein, Dimana Miteva, Karen Keeperman, Natalia Holot, Jose Alberto Nadal, Yinzhi Lai, Sadanand Vodala, Barbara Rosettani, Ana Carolina Giuseppi, Aylin Yucel, Pierre Fenaux
Journal: Leukemia (2023)
Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis
Authors: Jianfan Chen, Xueqing Xu, Song Chen, Ting Lu, Yingchun Zheng, Zhongzhi Gan, Zongrui Shen, Shunfei Ma, Duocai Wang, Leyi Su, Fei He, Xuan Shang, Huiyong Xu, Dong Chen, Leitao Zhang, Fu Xiong
Journal: International Journal of Oral Science (2023)

Abstract Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST , inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513 , a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1 . Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.
Digital Fellowships: Inspiring use of contemporary technologies in applied healthcare
Authors: Thomas Salisbury, Alexander T. Deng, Emily Burch, Alan Godfrey
Journal: npj Digital Medicine (2023)

The adoption of digital technologies in healthcare, accelerated by the COVID-19 pandemic, requires a well-prepared workforce capable of implementing those technologies. Here, we examine the role and impact of digital fellowships in facilitating digital transformation in healthcare systems. Digital fellowships are structured educational programmes designed to equip healthcare professionals with advanced digital skills. Focusing on UK-based initiatives like the Topol Digital Fellowship and the Fellowship in Clinical AI, we explore their efforts to prepare healthcare leaders for digital and AI adoption. Each fellowship programme provides participants with hands-on experience in digital healthcare projects and fosters interdisciplinary collaboration and post-fellowship support. We discuss how these fellowships contribute to staff retention by diversifying professional experiences and opportunities. We call for increased collaborations between universities, industry, and professional bodies to integrate lessons from digital fellowships into relevant curricula, acknowledging that digital fellowships are just one piece of the puzzle in bridging the digital skills gap in the healthcare workforce.
Author Correction: Cortical astrocytes modulate dominance behavior in male mice by regulating synaptic excitatory and inhibitory balance
Authors: Kyungchul Noh, Woo-Hyun Cho, Byung Hun Lee, Dong Wook Kim, Yoo Sung Kim, Keebum Park, Minkyu Hwang, Ellane Barcelon, Yoon Kyung Cho, C. Justin Lee, Bo-Eun Yoon, Se-Young Choi, Hye Yoon Park, Sang Beom Jun, Sung Joong Lee
Journal: Nature Neuroscience (2023)
Photothermal Excitation of Neurons Using MXene: Cellular Stress and Phototoxicity Evaluation
Authors: Yingqiao Wang, Jane E. Hartung, Adam Goad, Matías A. Preisegger, Benjamin Chacon, Michael S. Gold, Yury Gogotsi, Tzahi Cohen‐Karni
Journal: Advanced Healthcare Materials (2023)

Understanding the communication of individual neurons necessitates precise control of neural activity. Photothermal modulation is a remote and non-genetic technique to control neural activity with high spatiotemporal resolution. The local heat release by photothermally active nanomaterial will change the membrane properties of the interfaced neurons during light illumination. Recently, it is demonstrated that the two-dimensional Ti
The Iterative Mindset Method: a neuroscientific theoretical approach for sustainable behavior change and weight-loss in digital medicine
Authors: Kyra Bobinet, Stephanie M. Greer
Journal: npj Digital Medicine (2023)

Abstract With the growing prevalence of chronic conditions driving 85% of all healthcare costs, digital health offers a promising opportunity to reverse disease and improve health at-scale. The healthcare industry’s predominant approach to behavior change is performance-based with a focus on goals and tracking. This has not reversed the epidemic of chronic diseases and also can harm chronically ill and vulnerable patients via perceived failure-induced loss of motivation. Still nascent, the digital health industry is uniquely positioned to adopt and scale new and better behavior change approaches. In this paper, we present the theoretical foundation and initial findings of a neuroscience-based behavior change approach—what we call the Iterative Mindset Method TM . We discuss its promise, as a potentially more effective, neuroscience-based approach to changing health behaviors long-term, particularly in vulnerable populations. We conclude with avenues for future research.
Harnessing UBR5 for targeted protein degradation of key transcriptional regulators
Authors: Asad M. Taherbhoy, Danette L. Daniels
Journal: Trends in Pharmacological Sciences (2023)

Targeted protein degradation (TPD) has opened the door for drugging transcriptional regulators, yet the number of proteins targeted and E3 ligases utilized remain limited. Here, we highlight UBR5 and propose multiple strategies by which this E3 ligase could be modulated to drive degradation of key transcriptional targets implicated in disease.
Corrigendum to “EASL clinical practice guidelines on the management of hepatic encephalopathy” [J Hepatol 2022 (77) 807–824]
Authors: Sara Montagnese, Pierre-Emmanuelle Rautou, Manuel Romero Gómez, Fin Stolze Larsen, Debbie Shawcross, Dominique Thabut, Hendrik V Arenstorff Vilstrup, Karin Weissenborn
Journal: Journal of Hepatology (2023)
Expanded microbiome niches of RAG-deficient patients
Authors: Ryan A. Blaustein, Zeyang Shen, Sara Saheb Kashaf, ShihQueen Lee-Lin, Sean Conlan, Jim Thomas, James Mullikin, Alice Young, Gerry Bouffard, Betty Barnabas, Shelise Brooks, Chloe Buchter, Juyun Crawford, Joel Han, Shi-ling Ho, Richelle Legaspi, Quino Maduro, Holly Marfani, Casandra Montemayor, Karen Schandler, Brian Schmidt, Christina Sison, Mal Stantripop, Sean Black, Mila Dekhtyar, Cathy Masiello, Jenny McDowell, Morgan Park, Pam Thomas, Meg Vemulapalli, Marita Bosticardo, Ottavia M. Delmonte, Cassandra J. Holmes, Monica E. Taylor, Glenna Banania, Keisuke Nagao, Dimana Dimitrova, Jennifer A. Kanakry, Helen Su, Steven M. Holland, Jenna R.E. Bergerson, Alexandra F. Freeman, Luigi D. Notarangelo, Heidi H. Kong, Julia A. Segre
Journal: Cell Reports Medicine (2023)

The complex interplay between microbiota and immunity is important to human health. To explore how altered adaptive immunity influences the microbiome, we characterize skin, nares, and gut microbiota of patients with recombination-activating gene (RAG) deficiency-a rare genetically defined inborn error of immunity (IEI) that results in a broad spectrum of clinical phenotypes. Integrating de novo assembly of metagenomes from RAG-deficient patients with reference genome catalogs provides an expansive multi-kingdom view of microbial diversity. RAG-deficient patient microbiomes exhibit inter-individual variation, including expansion of opportunistic pathogens (e.g., Corynebacterium bovis, Haemophilus influenzae), and a relative loss of body site specificity. We identify 35 and 27 bacterial species derived from skin/nares and gut microbiomes, respectively, which are distinct to RAG-deficient patients compared to healthy individuals. Underscoring IEI patients as potential reservoirs for viral persistence and evolution, we further characterize the colonization of eukaryotic RNA viruses (e.g., Coronavirus 229E, Norovirus GII) in this patient population.
Hyperglycemia-regulated tRNA-derived fragment tRF-3001a propels neurovascular dysfunction in diabetic mice
Authors: Jun-Ya Zhu, Wen Yao, Xi-Sen Ni, Mu-Di Yao, Wen Bai, Tian-Jing Yang, Zi-Ran Zhang, Xiu-Miao Li, Qin Jiang, Biao Yan
Journal: Cell Reports Medicine (2023)

Neurovascular dysfunction is a preclinical manifestation of diabetic complications, including diabetic retinopathy (DR). Herein, we report that a transfer RNA-derived RNA fragment, tRF-3001a, is significantly upregulated under diabetic conditions. tRF-3001a downregulation inhibits Müller cell activation, suppresses endothelial angiogenic effects, and protects against high-glucose-induced retinal ganglion cell injury in vitro. Furthermore, tRF-3001a downregulation alleviates retinal vascular dysfunction, inhibits retinal reactive gliosis, facilitates retinal ganglion cell survival, and preserves visual function and visually guided behaviors in STZ-induced diabetic mice and db/db diabetic mice. Mechanistically, tRF-3001a regulates neurovascular dysfunction in a microRNA-like mechanism by targeting GSK3B. Clinically, tRF-3001a is upregulated in aqueous humor (AH) samples of DR patients. tRF-3001a downregulation inhibits DR-induced human retinal vascular endothelial cell and Müller cell dysfunction in vitro and DR-induced retinal neurovascular dysfunction in C57BL/6J mice. Thus, targeting tRF-3001a-mediated signaling is a promising strategy for the concurrent treatment of vasculopathy and neuropathy in diabetes mellitus.
Clinical development and management of adverse events associated with FGFR inhibitors
Authors: Vivek Subbiah, Srdan Verstovsek
Journal: Cell Reports Medicine (2023)

Approved fibroblast growth factor receptor (FGFR) inhibitors include erdafitinib, pemigatinib, and futibatinib. We review the most common toxicities associated with FGFR inhibitors and provide practical advice regarding their management. Hyperphosphatemia can be managed with careful monitoring, dose reduction or interruption, a prophylactic low-phosphate diet, and phosphate-lowering therapy. Ocular adverse events (AEs) are managed by withholding or adjusting the dose of the FGFR inhibitor. Dermatologic AEs include alopecia, which can be managed with minoxidil, and dry skin, which can be treated with moisturizers. Hand-foot syndrome can be prevented by lifestyle changes and managed with moisturizing creams, urea, or salicylic acid. Among gastrointestinal AEs, diarrhea may be managed with loperamide; stomatitis can be managed with baking soda rinses, mucosa-coating agents, and topical anesthetics; and dry mouth may be alleviated with salivary stimulants. Most FGFR inhibitor-associated toxicities are manageable with prophylactic measures and treatments; proactive monitoring is key to ensuring optimal clinical benefits.
Corrigendum to “EASL Clinical Practice Guidelines on haemochromatosis” [J Hepatol 2022 (77) 479–502]
Authors: Heinz Zoller, Benedikt Schaefer, Annick Vanclooster, Bill Griffiths, Edouard Bardou-Jacquet, Elena Corradini, Graça Porto, John Ryan, Markus Cornberg
Journal: Journal of Hepatology (2023)

EASL Clinical Practice Guidelines on haemochromatosisJournal of HepatologyVol. 77Issue 2PreviewHaemochromatosis is characterised by elevated transferrin saturation (TSAT) and progressive iron loading that mainly affects the liver. Early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy and other complications. In patients homozygous for p.Cys282Tyr in HFE, provisional iron overload based on serum iron parameters (TSAT >45% and ferritin >200 μg/L in females and TSAT >50% and ferritin >300 μg/L in males and postmenopausal women) is sufficient to diagnose haemochromatosis. Full-Text PDF It has come to our attention that there is an error in Table 1 of the published version of these clinical practice guidelines. The Table has been presented as below:Tabled 1LevelCriteriaSimple model for high, intermediate and low evidence1Systematic reviews (SR) (with homogeneity) of randomised controlled trials (RCT)Further research is unlikely to change our confidence in the estimate of benefit and risk2Randomised controlled trials (RCT) or observational studies with dramatic effects; systematic reviews (SR) of lower quality studies (i.e. non-randomised, retrospective)3Systematic reviews (SR) of lower quality studies (i.e. non-randomised, retrospective)Further research (if performed) is likely to have an impact on our confidence in the estimate of benefit and risk and may change the estimate4Case-series, case-control, or historically controlled studies (systematic review is generally better than an individual study)5Expert opinion (mechanism-based reasoning)Any estimate of effect is uncertain Open table in a new tab However, the Criteria for Level 3 are incorrect. The correct version of the Table is included below:Tabled 1LevelCriteriaSimple model for high, intermediate and low evidence1Systematic reviews (SR) (with homogeneity) of randomised controlled trials (RCT)Further research is unlikely to change our confidence in the estimate of benefit and risk2Randomised controlled trials (RCT) or observational studies with dramatic effects; systematic reviews (SR) of lower quality studies (i.e. non-randomised, retrospective)3Non-randomised controlled cohort/follow-up study/control arm of randomised trial (systematic review is generally better than individual study)Further research (if performed) is likely to have an impact on our confidence in the estimate of benefit and risk and may change the estimate4Case-series, case-control, or historically controlled studies (systematic review is generally better than an individual study)5Expert opinion (mechanism-based reasoning)Any estimate of effect is uncertain Open table in a new tab We apologise for any inconvenience caused.
The spectrum of glomerular and vascular kidney pathology associated with myeloproliferative neoplasms
Authors: Thibaut d’Izarny-Gargas, Pierre Isnard, Idris Boudhabhay, David Buob, Anissa Moktefi, Charel Linster, Aurélie Hummel, Emmanuel Esteve, Vincent Audard, Hélène Lazareth, Nadine Maroun, Alexandre Hertig, Clément Gosset, Charlotte Jouzel, Sarah Permal, Camille Domenger, Olivier Kosmider, Marion Rabant, Alexandre Karras, Jean-Paul Duong Van Huyen
Journal: Kidney International (2023)
PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants
Authors: Kathleen Baysac, Guangping Sun, Hiroto Nakano, Elizabeth G. Schmitz, Anthony C. Cruz, Charles Fisher, Alexis C. Bailey, Emily Mace, Joshua D. Milner, Michael J. Ombrello, Jordan K. Abbott, Juan Carlos Aldave Becerra, Eric J. Allenspach, Kristian Assing, T. Prescott Atkinson, Umair A. Bargir, Sarah K. Baxter, Jenna R.E. Bergerson, Ranjan Bista, Stephane Blanche, Lenore M. Buckley, Manish Butte, Benjamin Carcamo, Shanmukhaiah Chandrakala, Karin Chen, Sheva Chervinskiy, Ivan K. Chinn, Hey J. Chong, Kara E. Coffey, Andrew P. Copland, Edward W. Cowen, Guilhem Cros, Jean Jacques De Bruycker, Maria Teresa de la Morena, Mohammed Ehlayel, Lisa R. Forbes Satter, Erwin W. Gelfand, Olivier Gilliaux, Sara C. Glover, Mark Gorman, Thomas A. Griffin, Bodo Grimbacher, Alejandro A. Gru, Elie Haddad, Jerome Hadjadj, Joud Hajjar, Fabian Hauck, Timo Hautala, Steven M. Holland, Elena W.Y. Hsieh, Florence Ida Hsu, Emmanuel Jacquemin, Ankur Kumar Jindal, Stacy A. Kahn, Michael D. Keller, Roger H. Kobayashi, Christa Krupski, Allyson Larkin, Monica G. Lawrence, Manisha Madkaikar, Marion Malphettes, Timi Martelius, Mehek Mehta, Dean D. Metcalfe, Isabelle Meyts, Naveen Nannapaneni, J. Gonzalo Ocejo Vinyals, Kenneth Olivier, Amanda K. Ombrello, Jordan S. Orange, Nathan Rabinovitch, Christine K. Rauscher, Ann Redfern, Paul R. Reynolds, Frederic Rieux-Laucat, Elizabeth Secord, Filiz O. Seeborg, Mikko R.J. Seppänen, Irini Sereti, Daniel S. Shin, Junghee J. Shin, Scott B. Snapper, Deepti Suri, Sirikarn Tangcheewinsirikul, Akaluck Thatayatikom, Troy Torgerson, Fabien Touzot, Gulbu Uzel, Markku Varjosalo, Dewton F.P. Vasconcelos, Horst von Bernuth, Thomas Walsh, Jolan E. Walter, Brant R. Ward, Helmut Wittkowski, Christian A. Wysocki
Journal: Journal of Allergy and Clinical Immunology (2023)
In situ immunomodulation of tumors with biosynthetic bacteria promote anti-tumor immunity
Authors: Zhongda Lin, Fanqiang Meng, Yumeng Ma, Chi Zhang, Zhirang Zhang, Zhaoxin Yang, Yuan Li, Linlin Hou, Yuzhong Xu, Xin Liang, Xudong Zhang
Journal: Bioactive Materials (2023)

Immune checkpoint blockade (ICB) therapy potently revives T cell's response to cancer. However, patients suffered with tumors that had inadequate infiltrated immune cells only receive limited therapeutic benefits from ICB therapy. Synthetic biology promotes the alternative strategy of harnessing tumor-targeting bacteria to synthesize therapeutics to modulate immunity in situ. Herein, we engineered attenuated Salmonella typhimurium VNP20009 with gene circuits to synthetize granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 7 (IL-7) within tumors, which recruited dendritic cells (DCs) and enhanced T cell priming to elicit anti-tumor response. The bacteria-produced GM-CSF stimulated the maturation of bone marrow-derived dendritic cells (BMDCs), while IL-7 promoted the proliferation of spleen isolated T cells and inhibited cytotoxicity T cell apoptosis in vitro. Virtually, engineered VNP20009 prefer to colonize in tumors, and inhibited tumor growth by enhancing DCs and T cell infiltration. Moreover, the tumor-toxic GZMB+ CD8+ T cell and IFN-γ+ CD8+ T cell populations conspicuously increased with the treatment of engineered bacteria. The combination of GM–CSF–IL-7-VNP20009 with PD-1 antibody synergistically stunted the tumor progress and stasis.